Biomedical subjects

J A Castro

Publications and source records attributed to J A Castro.

At least 73 records · Page 4Linked to original sources

PubMed1995

[Approach to beliefs about health in 2 main health districts].

OBJECTIVE: To investigate whether doctors know users' beliefs about health and to investigate some of these beliefs. DESIGN: A crossover study. SETTING: The Cartuja and Almanjayar Health Centres in Granada. PATIENTS AND OTHER PARTICIPANTS: These were 204 users of the two centres, chosen at random and who attended for on-demand attention for whatever reason. Eleven patients refused the questionnaire. INTERVENTIONS: A 23-question questionnaire was administered during november and december 1993. MEASUREMENTS AND MAIN RESULTS: 64% were women and 36% men. Distribution by age and gender in both centres was similar. Coincidence (defined as 50% of replies totally in agreement and/or in agreement with the item in the questionnaire) between users' beliefs and doctors' opinions of those beliefs was slight (30%). Doctors' opinions concerning their patients' beliefs coincided with the beliefs shown by people with a lower educational level (F = 11.21, p < 0.00001) and over 45 years old (Sp = 0.25, p < 0.001). 70% thought that "illnesses are seen better on the screen"; and 57% that "if analysis and x-rays are not done, they don't feel satisfied". CONCLUSIONS: Doctors do not know their patients' health beliefs, attributing to the whole population the health beliefs of those who most consult the doctor. Users place great hopes in technology, with no relation to age, gender or educational level.

Adult↗

PubMed1995

Covalent binding of carbon tetrachloride reactive metabolites to liver microsomal and nuclear lipid and phospholipid classes from Sprague Dawley and osborne Mendel male rats.

The interaction between carbon tetrachloride (CCl4)-reactive metabolites and liver microsomal or nuclear lipids (covalent binding = CB) was studied in male rats from Osborne Mendel (OM) and Sprague Dawley (SD), strains with different cancer susceptibility. The in vitro or in vivo CB was more intense in OM than in SD. Most of the CB was with phospholipid (PL; SD > OM). The CB to cholesterol (CH) and cholesterol esters (CHE) was OM > SD. We also observed the presence of specific adducts only present in lipids from either OM or SD strains. The results were related to the well-known role of PL and CH derivatives in gene function control and cell growth.

Animals↗

PubMed1995

Trifluopromazine late preventive effects on carbon tetrachloride-induced liver necrosis.

Trifluopromazine (TFPro) administration to rats (50 mg/kg, ip) 30 min before or 6 or 10 hr after CCl4 treatment (1 ml/kg ip in olive oil) partially prevented necrogenic effects of this compound at 24 hr. TFPro has only minor effects on the covalent binding (CB) of CCl4-reactive metabolites to cellular constituents and even an enhancing action on CCl4-promoted lipid peroxidation (LP). Determination of TFPro levels in liver 1 and 3 hr after administration by gas chromatography/mass spectrometry showed its presence in that tissue at concentrations well above those needed for calmodulin (CaM) inhibitory effects of this drug. TFPro lowered body temperature in CCl4-treated animals during the 24-hr observation period. Protective effects of TFPro at 6 or 10 hr, when most of the CB and all of the LP has already occurred, suggest but do not prove a role for CaM in late stages of CCl4-induced necrogenic effects. Decreases in the body temperature of CCl4-poisoned animals provoked by TFPro might also play a role in the preventive actions of this drug.

Animals↗

PubMed1995

Radioprotectors as late preventive agents against carbon tetrachloride induced liver necrosis: protection by 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721).

Administration of the radioprotective agent 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) at 3 or 6 hr after carbon tetrachloride (CCl4) administration significantly prevented the liver necrosis produced by the hepatotoxin at 24 hr. It is well known that WR2721 does not exert or minimally exerts a protective activity by itself. The compound is activated through dephosphorylation to the free thiol WR1065, a process which is catalyzed by an alkaline phosphatase. We observed that this enzyme was widely distributed in the rat body. The WR2721 pretreatment 30 min before CCl4 administration modified the CCl4 levels reaching the liver at 1 hr of poisoning and exerted a significant increase in the covalent binding (CB) of 14CCl4-reactive metabolites to microsomal lipids at 3 hr. WR2721 did not modify the intensity of the CCl4-induced lipid peroxidation (LP) process at 1 or 3 hr of poisoning. CCl4-induced fat accumulation was not prevented when WR2721 was given 6 hr after CCl4. In fact, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.

Alkaline Phosphatase↗

PubMed1995

Proline interaction with trichloromethyl and trichloromethyl peroxyl free radicals in a model system: studies about the nature of the reaction products formed.

Trichloromethyl and trichloromethyl peroxyl radicals are known to be produced during CCl4 biotransformation and are considered to be critical for deleterious effects of this haloalkane. In this work we describe our studies on the interaction of both free radicals with a lipid-soluble derivative of the amino acid proline in a model system. The analysis of the reaction products formed by gas chromatography-mass spectrometry of the sylilated derivatives revealed the formation of at least 11 reaction products under anaerobic conditions and 13 under aerobic atmosphere. All of them were tentatively identified and all but 2 were proline analogs. Only 3 incorporated in their structure CCl3 or CCl2 portions of the CCl4 molecule and, consequently, most of the adducts formed would be missed during regular procedures most toxicologists use to determine CCl4. Results were analyzed in relation to the known role of proline in collagen metabolism and of this protein in liver cirrhosis.

Benzoyl Peroxide↗

PubMed1995

Reaction of bromotrichloromethane derived free radicals with uracil in a model system. Structures of products formed.

Free radicals generated by benzoyl peroxide-mediated catalytic decomposition of bromotrichloromethane (eg. trichloromethyl) were allowed to react under nitrogen or under air with uracil. Under nitrogen two reaction products were formed, one was identified as 5-chlorouracil and the other as a 5-bromouracil. Under air, besides the above two products other nine were also formed: 5,6-dihydrouracil; 5-hydroxyuracil; a chlorohydroxy adduct of uracil; a bromohydroxy derivative of uracil having the 5,6 bond in the saturated form; other bromohydroxy derivative of uracil having the double bond intact; 5,6-dihydroxyuracil; two dihalogenated hydroxylated uracil derivatives and one peak we were not able to descipher its structure. No single reaction product formed had carbon centered radicals (eg. trichloromethyl) added from CBrCl3 and consequently would be missed in 'in vivo' covalent binding studies where 14C haloalkane (CBrCl3 or carbon tetrachloride) were employed. If similar reaction products resulted during interaction of CBrCl3 reactive metabolites with uracil in RNAs, significant deleterious effects in their function would be expected. That possibility, however, remains to be established.

Aerobiosis↗

PubMed1995

Dithiothreitol inhibitory effects on carbon tetrachloride-promoted NADPH-dependent lipid peroxidation in liver microsomal suspensions.

In previous studies from our laboratory evidence was provided that generation in vivo of dithiothreitol (DTT) from DTT tetraacetate (DTTAC) was accompanied with preventive effects against CCl4-induced necrogenic effects on the liver. In that study, we reported the ability of treatment to decrease the intensity of covalent binding (CB) of the CCl4 reactive metabolites to cellular components but no evidence of preventive effects on CCl4-induced lipid peroxidation (LP) was obtained by the diene hyperconjugation technique. Now, we report that DTT at concentrations 1 or 3 mM inhibit at steps of the process after diene conjugation and prior to malondialdehyde formation. One of those steps might involve peroxides since we observed that DTT is able to significantly react with benzoyl peroxide in a model system. Others might also involve free radicals for in the present study we observed the reaction of DTT with trichloromethyl or trichloromethylperoxy free radicals generated from CBrCl3 in a model system. Reactions of DTT with free radicals and peroxides resulting in inhibition of CB and LP might be critical components in the preventive effects of DTTAC against CCl4-induced liver damage.

Animals↗

PubMed1995

Late protective effects of the anticalmodulin drug fluphenazine on carbon tetrachloride-induced liver necrosis.

Fluphenazine (FP) treatment (50 mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroxidation. FP lowered body temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts sufficient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature.

Animals↗

PubMed1994

[Hypertension programs and the risk of ischemic cardiopathy].

OBJECTIVE: To find the risk of ischaemic cardiopathy in a sample of hypertension patients. DESIGN: Crossover study. SETTING: Almanjáyar and Cartuja Health Centres (Granada). PATIENTS AND OTHERS TAKING PART: 202 Hypertension patients included in the programme and belonging to three practices in the above-mentioned centres. MEASUREMENTS AND MAIN RESULTS: We determined the variable of age, gender, overall cholesterol, cholesterol-HDL, TAS, HVI in ECG and we recorded the number of check-ups over the last year, tobacco consumption and diabetes. The 47% of men and 46% of women presented a RCI higher than that of the population as a whole for their age and gender group, in spite of treatment and intervention on these risk factors. Men between 45 and 64 presented higher RCI than women (p < 0.001) and had fewer check-ups. CONCLUSION: We consider that our programme did not sufficiently affect the prevention of ischaemic cardiopathy. It was especially deficient in the monitoring of men between 45 and 64 years. We think that the maintenance of programmes oriented round particular pathologies, instead of integrated programmes, is not sufficient to reduce ischaemic cardiopathy, which clearly has a multiple-cause origin.

Adult↗

PubMed1994

Late protective effects against CCl4-induced liver necrosis by the radioprotective agent 2-aminoethyl-isothiouronium bromide hydrobromide (AET).

Administration of the radioprotective agent 2-aminoethyl-isothiouronium bromide hydrobromide (AET) (240 mg/kg, i.p. in saline 30 min before or 6 or 10 h after CCl4 (1 ml/kg i.p. as a 20% v/v solution in olive oil) significantly prevented the necrogenic effect of the hepatotoxin at 24 h. Protection was more intense when the drug was given 6 h after CCl4 than when administered 30 min before. CCl4-induced fat accumulation was prevented only when AET was given 30 min before. AET did not prevent the CCl4-induced initiation of a lipid peroxidation (LP) process as evidenced by diene hyperconjugation of microsomal lipids. AET pretreatment 30 min before CCl4 did not significantly modify the CCl4 levels reaching the liver and only exerted a transient significant effect on the covalent binding of [14C]Cl4 reactive metabolites to microsomal lipids (CB) at 1 h but not at 3 h. The markedly intense protective effects of AET when given 6 or 10 h after CCl4 can not be attributed to decreased amounts of CCl4 reaching the liver or to decreasing effects in CB or to chain breaking effects in LP. Really, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.

Animals↗

PubMed1994

Nicotinamide late protective effects against carbon tetrachloride-induced liver necrosis.

Nicotinamide (NIC) is known to increase the synthesis of pyridine nucleotides and also to inhibit the hydrolysis of them to ADP-ribose, which in turn is involved in Ca2+ release from mitochondria via the ADP ribosylation of crucial mitochondrial proteins. In this work, we test the potential ability of NIC to be a late protective agent against CCl4-induced liver necrosis. We observed that 1 g/kg po NIC, 30 min before or 6 or 10 hr after CCl4 (1 ml/kg), given ip as a 20% (v/v) solution in olive oil, was able to significantly prevent the necrogenic effect of the hepatotoxin at 24 hr as evidenced by determination of isocitric dehydrogenase activity in plasma or by histological observation. NIC administration 6 hr after CCl4 prevented fatty liver induced by hepatotoxin at 24 hr. NIC did not modify CCl4-induced lipid peroxidation process at 1 hr after CCl4 and decreased the covalent binding of 14CCl4 to lipids. NIC decreased the levels of 14CCl4 reaching the liver when given 30 min before hepatotoxin but not when given 6 hr after it. NIC lowered body temperature of rats at 1, 3, and 6 hr and augmented it at 24 hr after CCl4. NIC concentrations in liver as determined by GC/MS/SIM analysis were 21 micrograms/g liver 1 hr after administration and 53 micrograms/g at 3 hr. Late preventive effects of NIC against CCl4 induced liver necrosis when given at 6 or 10 hr after CCl4 are compatible with the hypothesis that NIC restores mitochondrial ability for Ca2+ uptake. This hypothesis remains to be proved and is being further challenged in our laboratory.

Animals↗

PubMed1994

Decreased incorporation of 14C-leucine in different liver nuclear protein fractions at early stages of carbon tetrachloride poisoning in the rat.

Administration of CCl4 to 12-14 h starved Sprague Dawley male rats (220-240 g) at a dose of 5 ml of a 20% (v/v) olive oil solution/kg i.p. decreased the incorporation of 14C-leucine into microsomal and nuclear proteins at 1 or 2 h after the hepatotoxin. Decreased amino acid incorporation capacity in nuclear but not in microsomal proteins returned to control values at 4 h after poisoning. Cycloheximide given i.p. at a dose of 1 mg/kg in saline either alone or before CCl4 also decreased to a similar or greater extent the incorporation of 14C-leucine into both, microsomal and nuclear proteins at 1 h. The CCl4-induced decrease in amino acid incorporation was observable and significant even 1 h after CCl4 and involved histone and different non-histone nuclear protein fractions. Results suggest that decreased protein synthesis at the endoplasmic reticulum occurring in the very early stages of CCl4 poisoning might provoke temporary deficiencies in protein supplies to nuclei with as yet unknown consequences. However, some of the proteins involved have major regulatory properties in DNA expression.

Animals↗

PubMed1994

Interaction of trichloromethyl free radicals with thymine in a model system: a mass spectrometric study.

In previous studies from our laboratory we found that the CCl4 reactive metabolites produced during enzymatic in vitro or in vivo CCl4 biotransformation covalently bind to DNA. Further, chemically produced.CCl3 produce many adducts of unknown structure with the four DNA bases when the reaction proceeds in model systems. In the present work, we describe our attempt to elucidate by GLC/MS the structures of the adducts resulting when chemically generated.CCl3 interact with thymine. The following reaction products were identified: (i) 5-hydroxymethyl uracil; (ii) thymineglycol; (iii) 5-trichloroethyl uracil (tentative) and (iv) two isomeric 5,6-monochloro monohydroxy adducts of thymine (tentative). Reaction products found do not involve thymine positions directly participating in base-pairing processes. However, alterations in thymine structure reported if they occurred in DNA from livers of CCl4 poisoned animals, might potentially have biological significance that remains to be established.

Carbon Tetrachloride↗

PubMed1994

N-acetyl cysteine is an early but also a late preventive agent against carbon tetrachloride-induced liver necrosis.

N-Acetyl cysteine (NAC) treatment 30 min before or 6 or 10 h after carbon tetrachloride (CCl4) administration significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. NAC pretreatment was able to partially decrease the covalent binding of CCl4 reactive metabolites at 1 and 3 h of poisoning and, to a small extent, the concentration of CCl4 reaching the liver at 3 h. NAC also diminished partially the CCl4-promoted increases in lipid peroxidation at 3 h, but had an enhancing effect of its own of small intensity. Results suggest that early and late protective effects of NAC might be attributable to its prior conversion to cysteine and glutathione.

Acetylcysteine↗

PubMed1994

Reaction of 4-hydroxynonenal with some thiol-containing radioprotective agents or their active metabolites.

The rate of reaction of several radioprotective agents or their active metabolites with 4-hydroxynonenal (4HNE) was studied and compared to the rate of reaction with cysteine (Cys) and glutathione (GSH). The agents studied were: mercapto ethylamine (MEA); 2(3-aminopropyl) aminoethanethiol (WR1065); S-2-aminoethylisothiouronium bromide-hydrobromide (AET); 1,4-dithiothreitol (DTT); 1,4-dithioerythritol (DTE); N-2(2-mercaptopropionyl)-glycine (MPG); penicillamine hydrochloride (PA); N-acetylcysteine (NAC); 2-3 dimercapto-1 propane sulfonic acid (DMPS); 2,3-dimercaptopropanol (BAL), and meso 2,3 dimercapto succinic acid (DMS). All of them reacted with 4HNE. MEA and WR1065 were the most reactive thiols, and PA and DMS were the least reactive thiols. All the others reacted at rates comparable to or higher than that of cysteine or GSH. The potential role of this type of interactions in the protective action of these drugs against deleterious effects of radiation or carbon tetrachloride is analyzed.

Aldehydes↗

PubMed1994

5-methylcytosine attack by free radicals arising from bromotrichloromethane in a model system: structures of reaction products.

The interaction between free radicals derived from the catalytic decomposition of bromotrichloromethane and 5-methylcytosine (5MC) under different conditions were studied. The structures of the reaction products formed was established by the GC/MS analysis of their trimethylsilyl derivatives. Under anaerobic conditions, the formation of the following products was found: (1) thymine; (2) 5-hydroxymethyl uracil. Under aerobic conditions, the following reaction products were identified: (1) The same two products formed under anerobic conditions. (2) Monohydroxylated thymine. Precise location of the hydroxyl group was not established but probably corresponds to the six position isomer. (3) Two monochloro monohydroxy thymines. It is suggested that they are cis-trans isomers whose substituents are located at the 5-methyl and six positions of the base. (4) The trimethylsilyl derivative of thymine glycol. (5) Two monobromo monohydroxy adducts of thymine. One of them was detected as its underivatized form in the hydroxyl group position. (6) A partially silylated dihydroxythymine. When benzoyl peroxide was omitted from aerobic incubation mixtures, the compounds formed changed. No longer observable were: thymine; the two monochloro monohydroxy derivatives of thymine; thymine glycol, and one monohydroxythymine. On the other hand, two new reaction products were formed instead: a partially silylated monochloro-monohydroxy thymine and 5-hydroxymethyl-cytosine. If similar or equivalent reaction products were formed in DNA during CBrCl3 or CCl4 poisoning, results might be of relevance, because the 5MC content in DNA from eukaryotes is related to differentiation, gene control, and to carcinogenesis.

5-Methylcytosine↗

PubMed1994

Tyrosine attack by free radicals derived from catalytic decomposition of carbon tetrachloride.

The interaction between free radicals derived from the catalytic decomposition of carbon tetrachloride and tyrosine (the N-acetyl tyrosine ethyl ester, ATEE) under anaerobic and aerobic conditions was studied. The structure of the reaction products formed was deciphered by the GLC/MS analysis of their trimethylsilyl derivatives. Under anaerobic conditions the formation of the following products was found: (1) an unsaturated derivative of the amino acid; (2) the trimethylsilyl derivative of N-acetyl chloro tyrosine ethyl ester; (3) a hydroxyl adduct of ATEE; (4) an ATEE adduct having a chlorine and a CCl3 group in the molecule (it is suggested that CCl3 is attached to the benzyl carbon and the chlorine located in the benzene ring); (5) an ATEE adduct having only a CCl3 group tentatively assigned to be located on the benzyl carbon; and (6) and (7) were found to be two isomers of an ATEE having one CCl3 on the aromatic ring. Under aerobic conditions the following reaction products were identified: Two products which were similar to those numbered (1) and (2) and formed anaerobically; (8) and (11) two isomeric dichlorinated adducts of ATEE; (9) and (10) two isomeric dichlorinated monohydroxylated derivatives of ATEE. Concerning the potential relevance of these findings, we consider that if similar interactions to those here reported occurred during CCl4 poisoning, the activity of enzymes having tyrosine in their active center might result in impairment. Further, enzymes operating on tyrosine moieties in proteins might be perturbed in their action tyrosine groups were attacked by the free radicals arising from catalytic decomposition of CCl4 evidenced here.

Aerobiosis↗

PubMed1994

Serum protein polymorphism in Chuetas (Majorcan Jews)--GC, A2HS, ORM, ITI and HP.

A sample of 140 Chuetas (descendants of Majorcan Jews) were typed for the GC, A2HS, ORM, ITI and HP serum proteins. Studies on ORM and ITI markers have not yet been reported in other Jewish populations. The allele frequencies obtained were: GC*1 = 0.610; A2HS*1 = 0.787; ORM*F1 = 0.339; ORM*S = 0.497; ITI*1 = 0.581; ITI*2 = 0.414; HP*2FS = 0.625; HP*1S = 0.230; HP*1F = 0.135. Some rare variants were found in polymorphic frequencies (ORM*S1 = 0.043; ORMS*S2 = 0.096; A2HS*10 = 0.015). These results have been compared with those found in other Jewish and non-Jewish European populations. The relatively high frequency of the HP*2FS allele and the presence of ORM*S1 and ORM*S2 variants in Chuetas show the Jewish origin of this population. The frequencies of GC and A2HS in Chuetas are similar to those found in other surrounding non-Jewish populations. ITI results are similar to those found in the two European populations studied. HP frequencies suggest a Spanish admixture.

Alpha-Globulins↗